Tetrahedron Letters 54 (2013) 5751–5754

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Tetrahedron Letters

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Rapid access to the synthesis of polysubstituted d-lactones viatandem stereoselective conjugate addition/a-alkylation ofunsaturated 7,3-lactone-a-D-xylofuranose derivative

0040-4039/$ - see front matter � 2013 Elsevier Ltd. All rights reserved.http://dx.doi.org/10.1016/j.tetlet.2013.08.036

⇑ Corresponding authors. Tel.: +52 222 2295500/7391; fax: +52 222 2454972.E-mail address: fernando.sartillo@correo.buap.mx (F. Sartillo-Piscil).

O

NN

O

(+)-Scholarisine A

OO

OO

OO

O

Limonin

H

H

O

O

OH

OH

OH

OHO

O

H2N

(+)-Discodermolide

Figure 1. Biological important compounds containing the polysubstilactone fragment.7

Elsie Ramírez, Leticia Quintero, Rosa L. Meza-León, Martha Sosa-Rivadeneyra, Silvano Cruz-Gregorio ⇑,Fernando Sartillo-Piscil ⇑Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla (BUAP), 14 Sur Esq. San Claudio, San Manuel, 72570 Puebla, Mexico

a r t i c l e i n f o

Article history:Received 9 July 2013Revised 7 August 2013Accepted 10 August 2013Available online 16 August 2013

Keywords:Conjugate additionStereoselectivityd-LactonesCarbohydratesTandem

a b s t r a c t

a-D-xylo-7,3-Unsaturated lactone, a versatile chiral building block, undergoes Cu-catalyzed conjugatedaddition with high yield and stereoselectivity. When the conjugated reaction is quenched with a suitablealkyl halide, a tandem stereoselective conjugated/a-alkylation reaction is achieved. Further, selectivehydrolysis of the 1,2-O-isopropylidene moiety followed by oxidative cleavage and reduction reaction,afforded the title compounds.

� 2013 Elsevier Ltd. All rights reserved.

O

tuted d-

Conjugate addition (sometimes known as the Michael addition),probably represents the best way for introducing a nucleophile inthe b-position of an unsaturated carbonyl compound.1 As thisnucleophilic introduction affords an incipient enolate intermedi-ate, the chemical reaction can be quenched by a suitable electro-phile and thus turns this reaction into a sequential or tandemtransformation that, not only allows the incorporation of two func-tional groups during the same chemical transformation, but canalso be done under enantio-and diastereoselective fashion.2

Regarding the diastereoselective conjugated addition (DCA),3 theuse of chiral auxiliary4 and chiral substrates5 have proven to betwo powerful tools which provide optical purity at low cost; espe-cially if the source of chirality comes from carbohydrates (chiralpool).

During the course of a project designed to synthesize biologi-cally important lactones, the preparation of novel optically purepolysubstituted d-lactones was required; those by the way, arecommon fragments in many biologically important compounds(Fig. 1).6 For that reason, we report here a rapid and efficient meth-odology for the synthesis of the required lactones based on theDCA-and the tandem DCA/a-alkylation reaction by taking advan-tage of the chiral substrate approach.5,8 To this end, a DCA reaction

of the unsaturated 7,3-d-lactone-a-D-xylofuranose derivative 1was planned. Once the DCA methodology is set up, we will try totrap the enolate intermediate with alkyl halides to thus developinga tandem DCA/a-alkylation reaction.

Finally, by conducting a selective hydrolysis of the 1,2-O-isopro-pyliden moiety of the DCA/a-alkylation products, followed by oxi-dative cleavage of the respective 1,2-diols; and the reduction of theformed dicarbonyl compounds with NaBH4, the required polysub-stituted d-lactones will be obtained (Fig. 2). This simple strategymay result to be attractive because the preparation of the chiral

Table 2Stereoselective a-alkylation of enolate 3

O

O

O

OBrMgO

R1

3 4

2 equiv of R2X-40 °C to rt

O

O

O

OO

R1

R2

Entry R1 R2X Yielda (%)

1 p-F-Ph CH3I 652 p-F-Ph BnBr 633 p-F-Ph Allyliodide 684 Bn Allyliodide 63

a Yields after chromatographic purification.

O

O

O

OO

O O

RNu

HO

HO

optically purepolysubstituted δ -lactones

CA

or tandem

CA/α-alkyl

ationhydrolysis

dehomologation/reduction

1

Figure 2. Strategy for the synthesis of polysubstituted lactones.

4(R1 = p-F-Ph; R2 = allyl)

O

O

O

OO

R1

R2 OR2

R1

O

H4

OH3H5

H6

O

H4

H6

R2H3

OR1

H5

OH4

H3

NOE3JH5-H6 = 12.0 Hz3JH4-H5 = 3.9 Hz

4C 4T

Figure 3. Stereochemistry and conformational preference of d-lactone 4.

5752 E. Ramírez et al. / Tetrahedron Letters 54 (2013) 5751–5754

synton 1 is rapidly achieved (in multi gram-scale) from diacetone-D-glucose in a sequential hydrolysis–oxidation–Wittig olefination(SHOWO protocol9) featuring a highly diastereoselective Wittigolefination reaction in aqueous media.9c

Because the high efficiency of the Cu-catalyzed DCA of Grignardreagents to a,b-unsaturated esters (and related compounds) is wellrecognized;3a the present work begins with the treatment of lac-tone 1 with of p-F-PhMgBr and CuBrSMe2. The use of higheramounts of Cu catalyst or Grignard reagent (e.g., 10 equiv of RMgBrand 5 equiv of CuBrSMe2),10 as well as additional additives (TMSCl,LiBr, HMPA)11 was not necessary, since only 0.5 equiv of CuBrSMe2

and 2 equiv of the Grignard reagent at �40 �C was more than en-ough to obtain high yield and high anti-stereoselectivity (see en-tries 1 and 2).12

The use of CuI as catalyst was less effective than CuBrSMe2 (en-try 3); therefore the CuBrSMe2 catalyst was used for the otherexperiments. With ethyl, methyl and benzyl Grignard reagents (en-tries 4–6) the DCA products were obtained with high yields (75–85%) and stereoselectivity (96%); however, only 8% yield of theDCA product was obtained for the case of allylMgCl (entry 7), oronly a trace was observed when CuI was used (entry 8). In thesetwo latter cases, the 1,2-addition compound (not shown) was ob-tained as the major product (Table 1).

Having set up an efficient protocol for the DCA of lactone 1, wethen focused on the tandem protocol. Thus, the reaction mixture ofDCA (with p-F-PhMgBr and BnMgCl as Grignard reagents, and CuB-rSMe as catalyst) at �40 �C was treated with selected alkyl halides(CH3I, BnBr, and allyliodide) and stirred at room temperature for3 h.13 The expected a-alkylation proceeded with moderated yields(63–70%); however, only one stereoisomer was isolated after chro-matographic purification (Table 2). The analysis of representativecoupling constants and selected 2D-NOESY interactions of lactone4 (R1 = p-F-Phenyl, R2 = allyl) indicates that both substituents aretrans-oriented with a boat-twisted conformation 4T for the d-lac-tone ring (Fig. 3). The large value of vicinal coupling constant(3JH5-H6 = 12.0 Hz), and the smaller 3JH4-H5 value (3.9 Hz) confirms

Table 1Diastereoselective conjugated addition (DCA) to lactone 1

O

O

O

OO

O

O

O

OO

R

Conditions

1 22 equiv of RMgBr0.5 equiv of Cu

Entry RMgX Yield (%) de (%)

1 p-F-PhMgBr CuBrSMe2, THF at 0 �C 78 802 p-F-PhMgBr CuBrSMe2, THF at �40 �C 88 973 p-F-PhMgBr CuI, THF at 0 �C 52 904 EtMgBr CuBrSMe2, THF at �40 �C 85 965 CH3MgBr CuBrSMe2, THF at �40 �C 75 966 BnMgCl CuBrSMe2, THF at �40 �C 82 967a AllylMgCl CuBrSMe2, THF at �40 �C 8 —8a AllylMgCl CuI, THF at �40 �C Trace —

a 1,2-Addition compared as major product.

the anti-relationship between H5 and H6 and the pseudo diequato-rial relationship between H4 and H5, respectively. Because all ofthe d-lactones possess very similar coupling constants, it can be as-sumed that all of them enjoy the same major conformation 4T. Thestereochemical outcome of a-alkylation of the enolates is consis-tent with models previously proposed either in cyclic or acyclicsystems.2,14

We finally proceeded to transform the d-lactones 4a–c into thedesired polysubstituted d-lactones 7a–c. Selective hydrolysis of the1,2-O-isopropyliden moiety with a mixture of acetic acid/sulfuricacid at room temperature afforded the respective 1,2-diols 5 whichwere treated with an aqueous solution of NaIO4 at 0 �C to obtainthe dicarbonyl compounds 6, and finally, with the reduction of 6with NaBH4, the polysubstituted d-lactones 7 were prepared inmodest overall yields (Scheme 1).15

4a (R = Me)4b (R = Bn)4c (R = allyl)

O

O

O

OO

R CH3CO2H

O

OH

OH

OO

R

NaIO4

O

OOO

R

O

NaBH4

OHO

HO R

O

5

6

F F

F

F

7a (R = Me): 32%7b (R = Bn): 45%7c (R = allyl): 32%

H2SO4

Scheme 1. Preparation of polysubstituted d-lactones.

E. Ramírez et al. / Tetrahedron Letters 54 (2013) 5751–5754 5753

In conclusion, a fast and accessible stereoselective protocol wasdeveloped for the preparation of optically pure polysubstituted d-lactones16 featuring a tandem diastereoselective conjugated addi-tion/a-alkylation reaction. Applications of this methodology tothe synthesis of biologically active lactones are in progress.

Acknowledgments

We gratefully acknowledge financial support from CONACyT(CB-2012/179074) and Benemérita Universidad Autónoma de Pue-bla (BUAP-VIEP).

References and notes

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3. (a) Harutyunyan, S. R.; Hartog, T.; Geurts, K.; Minnaard, A. J.; Feringa, B. L. Chem.Rev. 2008, 108, 2824; (b) Rossiter, B. E.; Swingle, N. M. Chem. Rev. 1992, 92, 771.

4. (a) Seebach, D.; Beck, A. K.; Heckel, A. Angew. Chem., Int. Ed. 2001, 40, 92; (b)Helmchen, G.; Wegner, G. Tetrahedron Lett. 1985, 26, 6047; (c) Mukaiyama, T.;Iwasawa, N. Chem. Lett. 1981, 913; (d) Oppolzer, W.; Mills, R. J.; Pachinger, W.;Stevenson, T. Helv. Chim. Acta 1986, 69, 1542.

5. (a) Cluzeau, J.; Lubell, W. D. J. Org. Chem. 2004, 69, 1504; (b) Nadein, O. N.;Kornienko, A. Org. Lett. 2004, 6, 831; (c) Manpadi, M.; Kornienko, A. TetrahedronLett. 2005, 46, 4433; (d) Kireev, A. S.; Manpadi, M.; Kornienko, A. J. Org. Chem.2006, 71, 2630; (e) Rastogi, S. K.; Kornienko, A. Tetrahedron: Asymmetry 2006,17, 3170; (f) Pearson, A. J.; Protasiewicz, J. D.; Updegraff, J.; Zhang, M.Tetrahedron Lett. 2007, 48, 5569.

6. (a) Gesson, J. P.; Jacquesy, J. C.; Mondon, M. Tetrahedron Lett. 1987, 28, 3945; (b)Gesson, J. P.; Jacquesy, J. C.; Mondon, M. Tetrahedron 1989, 45, 2627; (c)Bessodes, M.; Benamghar, R.; Antonakis, K. Carbohydr. Res. 1990, 200, 493; (d)Dongsoo, K. Agric. Chem. Biotechnol. 2005, 49, 62–64; (e) Baskaran, S.; Vasu, J.;Kodukulla, R. P. K.; Trivedi, G. K. Tetrahedron 1996, 52, 4515; (f) Subramanian,B.; Griski, K. T. J. Chem. Res. 1995, 308; (g) Tadano, K.-I.; Shimada, K.-I.; Miyake,A.; Ishihara, J.; Ogawa, S. Bull. Chem. Soc. Jpn. 1989, 62, 3978.

7. (a) Cai, X. H.; Tan, Q. G.; Liu, Y. P.; Feng, T.; Du, Z. Z.; Li, W. Q.; Luo, X. D. Org. Lett.2008, 10, 577; (b) Rosenfeld, R.; Hofmann, K. J. Am. Chem. Soc. 1951, 73, 2491;(c) Gunasekera, S. P.; Cranick, S.; Longley, R. E. J. Nat. Prod. 1989, 52, 757.

8. Hanessian, S. Total Synthesis of Natural Products: The ‘Chiron’ Approach;Pergamon Press: Oxford, 1985.

9. (a) Sartillo-Piscil, F.; Vargas, M.; Anaya de Parrodi, C.; Quintero, L. TetrahedronLett. 2003, 44, 3919; (b) Reddy, L. V. R.; Reddy, P. V.; Shaw, A. K. Tetrahedron:Asymmetry 2007, 18, 542; (c) Ramirez, E.; Meza-Leon, R.; Quintero, L.; Sartillo-Piscil, F. Tetrahedron Lett. 2010, 51, 2178; (d) Sidnei, M.; Ligeour, T. C.; Caroline,L.; Christine, G.; Delphine, J.; Emanuelle, D.; Francoise, D. Green Chem. 2011, 13,1812; (e) Venkat, R. P.; Vikas, B.; Brijesh, K.; Shaw, A. K. Eur. J. Org. Chem. 2011,1575.

10. (a) Totani, K.; Nagatsuka, T.; Takao, K.-I.; Ohba, S.; Tadano, K.-I. Org. Lett. 1999,1, 1447; (b) Totani, K.; Nagatsuka, T.; Yamaguchi, S.; Takao, K.-I.; Ohba, S.;Tadano, K.-I. J. Org. Chem. 2001, 66, 5965.

11. (a) Hanessian, S.; Gai, Y.; Wang, W. Tetrahedron Lett. 1996, 37, 7473; (b)Hanessian, S.; Wang, W.; Gai, Y. Tetrahedron Lett. 1996, 37, 7477; (c) Raczko, J.Tetrahedron: Asymmetry 1997, 8, 3821; (d) Han, G.; Hruby, V. J. Tetrahedron Lett.2001, 42, 4281.

12. General procedure for the conjugate addition. A mixture of Grignard reagentsolution (0.94 mmol) and copper (I) bromide–dimethyl sulfide complex(48.3 mg, 0.24 mmol) was stirred at room temperature for 1 h. Then, lactone1 (100.0 mg, 0.47 mmol) dissolved in dried THF (3 mL) was added to thereaction mixture at �40 �C. The resulting mixture was stirred for 3 h. After thereaction was completed, the reaction mixture was quenched with a saturatedsolution of ammonium chloride, and extracted with EtOAc (3 � 20 mL). Theresidue was purified through column chromatography (silica, eluent: mixtureof hexane and ethyl acetate).2 (R = Me): as a yellow syrup, 80.5 mg (75%). [a]25 +16.0 (CHCl3, c 1.0). 1H NMR(400 MHz, CDCl3) d: 1.16 (d, J = 7.6 Hz, 1H), 1.34 (s, 3H), 1.52 (s, 3H), 2.25 (dd,J = 16.8, 5.2 Hz, 1H), 2.41 (m, 1H), 2.77 (dd, J = 16.8, 5.2 Hz, 1H), 4.25 (t,J = 3.3 Hz, 1H), 4.72 (m, 2H), 5.95 (d, J = 3.6 Hz, 1H). 13C NMR (100 MHz, CDCl3)d: 17.9, 26.2, 26.6, 28.7, 32.9, 77.5, 81.9, 83.8, 104.8, 112.2, 169.2. HRMS-EI (m/z): [M]+ calcd for C11H16O5 228.0998; found 228.1027.2 (R = Et): as a yellow syrup, 96.8 mg (85%). [a]25 +17.2 (CHCl3, c 1.0). 1H NMR(400 MHz, CDCl3) d: 1.03 (t, J = 7.6 Hz, 3H), 1.34 (s, 3H), 1.52 (m, 3H), 1.25–1.60(m, 2H), 2.14 (m, 1H), 2.26 (dd, J = 16.8, 6.8 Hz, 1H), 2.71 (dd, J = 16.8, 5.6 Hz,1H), 4.31 (t, J = 3.6 Hz, 1H), 4.66 (d, J = 3.2 Hz, 1H), 4.73 (d, J = 4.0 Hz, 1H), 5.95(d, J = 3.6 Hz, 1H). 13C NMR (100 MHz, CDCl3) d: 11.4, 25.8, 26.2, 26.6, 26.7,31.4, 35.9, 76.6, 82.0, 83.6, 104.7, 112.1, 169.8. HRMS-EI (m/z): [M]+ calcd forC12H18O5 242.1154; found 242.1119.2-(R = p-F-phenyl): as a yellow syrup, 127.5 mg (88%). [a]25 �4.7 (CHCl3, c 1.0).1H NMR (400 MHz, CDCl3) d: 1.32 (s, 3H), 1.47 (s, 3H), 2.70 (dd, J = 16.8, 6.6 Hz),2.99 (dd, J = 16.8, 6 Hz, 1H), 3.52 (q, J = 6.0, 4.2 Hz, 1H), 4.46 (t, J = 3.6 Hz, 1H),4.61 (d, J = 3.0 Hz, 1H), 4.75 (d, J = 3.9 Hz, 1H), 6.01 (d, J = 3.6 Hz, 1H), 7.06 (m,

2H), 7.21 (m, 2H). 13C NMR (100 MHz, CDCl3) d: 26.1, 26.5, 31.3, 39.1, 78.4,81.8, 83.5, 104.9, 112.3, 116.2 (d, J = 20.6 Hz), 128.5 (d, J = 8.0 Hz), 135.1 (d,J = 3.4 Hz), 162.1 (d, J = 246 Hz), 169.3. HRMS-EI (m/z): [M]+ calcd forC16H17FO5 308.1060; found 308.1075.2 (R = Bn): as a yellow syrup, 117.3 mg (82%). [a]25 +2.6 (CHCl3, c 1.0). 1H NMR(400 MHz, CDCl3) d: 1.33 (s, 3H), 1.47 (s, 3H), 2.26 (dd, J = 16.8, 5.2 Hz, 1H),2.54–2.69 (m, 3H), 2.89 (dd, J = 12.8, 5.6 Hz, 1H), 4.35, (dd, J = 3.2, 3.2 Hz, 1H),4.34 (d, J = 3.6 Hz, 1H), 4.75 (d, J = 3.2 Hz, 1H), 5.95 (d, J = 3.6 Hz, 1H), 7.15–7.34(m, 5H). 13C NMR (100 MHz, CDCl3) d: 26.2, 26.6, 30.6, 35.9, 38.7, 76.2, 82.0,83.8, 104.6, 112.3, 126.9, 128.8, 137.4, 169.3. HRMS-EI (m/z): [M]+ calcd forC17H20O5 304.1311; found 304.1341.2 (R-allyl): as a yellow syrup, 9.5 mg (8%). [a]25 +3.0 (CHCl3, c 0.7). 1H NMR(400 MHz, CDCl3) d: 1.34 (s, 3H), 1.51 (s, 3H), 2.15–2.35 (m, 4H), 2.71 (dd,J = 15.9, 4.8 Hz, 1H), 4.32 (dd, J = 3.3, 3.3 Hz, 1H), 4.67 (d, J = 3.0 Hz, 1H), 4.73 (d,J = 3.9 Hz, 1H), 5.12 (dm, J = 8.1 Hz, 1H), 5.17 (br s, 1H), 5.75 (m, 1H), 5.94 (d,J = 3.6 Hz). 13C NMR (100 MHz, CDCl3) d: 26.2, 26.6, 29.7, 31.1, 33.7, 36.9, 76.4,81.9, 83.7, 104.6, 112.3, 118.6, 133.8, 169.4.

13. General procedure for the tandem conjugate addition/a-alkylation. A mixture ofGrignard reagent solution (0.94 mmol) and copper (I) bromide–dimethylsulfide complex (0.24 mmol) was stirred at room temperature for 1 h. Then,a solution of lactone 1 (100.0 mg, 0.47 mmol) in dried THF (3 mL) at �40 �Cwas added to the reaction mixture. The resulting mixture was stirred for 3 hbefore adding the respective alkyl halide (1.41 mmol). The reaction mixturewas warmed to room temperature and stirred for 2.5 hours. The reactionmixture was quenched with a saturated solution of ammonium chloride, andextracted with EtOAc (3 � 20 mL).4 (R1 = p-F-Ph, R2 = Me): as a white solid, 90.9 mg (60%). Mp = 145 �C. [a]25

+41.9 (CHCl3, c 1.0). 1H NMR (400 MHz, CDCl3) d: 1.0 (d, J = 6.6 Hz, 1H), 1.32 (s,3H), 1.43 (s, 3H), 2.60 (m, 1H), 2.85 (dd, J = 12.9, 4.5 Hz, 1H), 4.56 (dd, J = 3.9,3.3 Hz, 1H), 4.78 (d, J = 3.0 Hz, 1H), 4.82 (d, J = 3.9 Hz, 1H), 5.97 (d, J = 3.6 Hz,1H), 7.08 (m, 2H), 7.18 (m, 2H). 13C NMR (100 MHz, CDCl3) d: 13.55, 26.06,26.5, 38.7, 48.5, 80.7, 82.3, 83.0, 104.6, 112.2, 116.1 (d, J = 21.7 Hz), 129.2 (d,J = 9.1 Hz), 136.4 (d, J = 3.4 Hz), 162.1 (d, J = 244.8 Hz), 173.2. HRMS-EI (m/z):[M]+ calcd for C17H19FO5 322.1217; found 322.1179.4 (R1 = p-F-Ph, R2 = Bn): as a yellow syrup, 112.3 mg, (60%). [a]25 +55.8 (CHCl3, c1.1). 1H NMR (400 MHz, CDCl3) d: 1.31 (s, 3H), 1.42 (s, 3H), 2.63 (dd, J = 14.0,4.0 Hz, 1H), 2.86 (m, 1H), 3.08 (m, 2H), 4.50 (t, J = 3.6 Hz, 1H), 4.74 (d, J = 2.8 Hz,1H), 4.79 (d, J = 4.0 Hz, 1H), 5.97 (d, J = 3.6 Hz, 1H), 7.06 (m, 4H), 7.14 (m, 5H).13C NMR (100 MHz, CDCl3) d: 26.0, 26.5, 34.3, 46.0, 80.7, 81.5, 83.0, 104.6,112.2, 116.2 (d, J = 21.3 Hz), 126.4, 128.3, 129.2, 129.4 (d, J = 7.5 Hz), 136.3 (d,J = 3.4 Hz), 139.1, 162.1 (d, J = 244.9 Hz), 172.1. HRMS-EI (m/z): [M]+ calcd forC23H23FO5 398.1530; found 398.1492.4-(R1 = p-F-Ph, R2 = allyl): as a yellow syrup, 106.4 mg (65%). [a]25 +38.2 (CHCl3,c 1.1). 1H NMR (400 MHz, CDCl3) d: 1.32 (s, 3H), 1.42 (s, 3H), 2.18 (m, 1H), 2.30(m, 1H), 2.67 (m, 1H), 3.07 (dd, J = 12.0, 3.9 Hz, 1H), 4.50 (t, J = 3.6 Hz, 1H), 4.77(d, J = 2.7 Hz, 1H), 4.80 (d, J = 3.9 Hz, 1H), 4.85 (dm, J = 17.4 Hz, 1H), 5.01 (dm,J = 10.2 Hz, 1H), 5.80 (m, 1H), 5.96 (d, J = 3.6 Hz, 1H), 7.07 (m, 2H), 7.17 (m, 2H).13C NMR (100 MHz, CDCl3) d: 26.0, 26.4, 31.9, 43.1, 45.2, 80.6, 82.0, 83.0, 104.5,112.2, 116.0 (d, J = 21.6 Hz), 118.2, 129.3 (d, J = 7.9 Hz) 134.0, 136.1 (d,J = 3.4 Hz), 162.1 (d, J = 246.0 Hz), 172.0. HRMS-FAB (m/z): [M]+ calcd forC19H21FO5 348.1373; found 348.1402.4 (R1 = Bn, R2 = allyl): as a yellow syrup, 97 mg (60%). [a]25 +14.5 (CHCl3, c 1.0).1H NMR (400 MHz, CDCl3) d: 1.29 (s, 3H), 1.39 (s, 3H), 2.34 (dd, J = 13.2, 6.0 Hz,1H), 2.50 (m, 2H), 2.64 (dd, J = 13.8, 8.7 Hz, 1H), 2.90 (dd, J = 13.5, 6.3 Hz, 1H),4.32 (t, J = 2.4 Hz, 1H), 4.62 (d, J = 2.4 Hz, 1H), 4.69 (d, J = 3.9 Hz, 1H), 5.09 (br s,1H), 5.14 (dm, J = 5.7 Hz, 1H), 5.72 (m, 1H), 5.83 (d, J = 3.9 Hz, 1H), 7.17 (m, 2H),7.29 (m, 3H). 13C NMR (100 MHz, CDCl3) d: 26.3, 26.4, 34.4, 37.7, 38.6, 41.6,76.3, 80.5, 83.2, 104.2, 112.3, 118.1, 127.0, 128.7, 129.2, 134.6, 137.4, 172.0.

14. Shintani, R.; Tokunaga, N.; Doi, H.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 6240.15. To a solution (3 mL) made of a mixture of acetic acid (46%), sulfuric acid (16%),

and water (38%) was added therespective lactone 4 (0.31 mmol) and allowedto react for 2.5 h (monitored by tlc) at room temperature. Then, the reactionmixture was neutralized with a saturated solution of sodium carbonate andextracted with EtOAc (3 � 20 mL). The organic phase was concentrated underthe reduced pressure and dissolved in THF (2 mL), and sodium periodate(0.4 mmol) was added. The reaction mixture was stirred for 40 min, and theformed solids were filtered and the organic phase was concentrated underreduced pressure giving the respective aldehyde 6 as a yellow oil. Compound 6was dissolved in THF (2 ml) and H2O (0.5 mL) and sodium borohydride(0.46 mmol) was added. The reaction mixture was stirred at 0 �C for 1 h beforeadding water (1 mL), and the THF was evaporated under reduced pressure andthe residue was extracted with ethyl acetate (3 � 20 ml). The organic phasewas evaporated and the residue was purified by chromatography on silica gel(hexane/ethyl acetate).Compound 7a: as a colorless liquid, 32%, [a]25 �84.5 (CHCl3, c 0.9). 1H NMR(400 MHz, CDCl3) d: 1.22 (d, J = 6.9 Hz, 3H), 3.40 (m, 2H), 3.55 (m, 2H), 3.69 (dd,J = 11.1, 7.5 Hz, 1H), 4.53 (dd, J = 8.4, 1.2 Hz, 1H), 7.08 (m, 2H), 7.35 (m, 2H). 13CNMR (100 MHz, CDCl3) d: 14.2, 38.1, 51.8, 63.9, 69.6, 80.4, 115.9 (d, J = 20.5 Hz),129.9 (d, J = 7.9 Hz), 130 (d, J = 3.37 Hz), 162.2 (d, J = 246.0 Hz), 179.7.Compound 7b: As a yellow liquid (45%). [a]25 �76.2 (CHCl3, c 1.0). 1H NMR(400 MHz, CDCl3) d: 2.94 (dd, J = 14.0, 5.2 Hz, 1H), 3.01 (dd, J = 14.0, 5.2 Hz, 1H),3.35 (dd, J = 7.2, 4.4 Hz, 1H), 3.54 (m, 2H), 3.68 (m, 2H), 4.37 (dd, J = 8.4, 0.8 Hz,1H), 7.02 (m, 4H), 7.20 (m, 5H). 13C NMR (100 MHz, CDCl3) d: 14.2, 34.1, 44.5,47.6, 63.9, 69.7, 80.4, 115.6 (d, J = 20.5 Hz), 126.7, 128.4, 129.7, 130.1 (d,J = 7.9 Hz), 130.6, 137.0, 162.1 (d, J = 245.8 Hz), 178.2. HRMS-EI (m/z): [M]+

calcd for C19H19FO4 330.1267; found 330.1245.

5754 E. Ramírez et al. / Tetrahedron Letters 54 (2013) 5751–5754

Compound 7c: As a yellow liquid (40%). [a]25 �76.7 (CHCl3, c 1.0). 1H NMR(400 MHz, CDCl3) d: 2.39 (m, 1H), 2.49 (m, 1H), 3.40 (m, 1H), 3.46 (m, 1H), 3.58(m, 1H), 3.69 (m, 1H), 4.50 (d, J = 8.4 Hz, 1H), 4.99 (d, J = 8.4 Hz, 1H), 5.03 (br s,1H), 5.55 (m, 1H), 7.06 (t, J = 8.6 Hz, 2H), 7.35 (m, 2H). 13C NMR (100 MHz,CDCl3) d: 32.9, 43.0, 48.2, 63.9, 69.7, 80.5, 115.81 (d, J = 21.2 Hz), 118.6, 130.1(d, J = 7.6 Hz), 130.80 (d, J = 3.1 Hz), 133.5, 162.2 (d, J = 244.4 Hz), 178.2. HRMS-EI (m/z): [M]+ calcd for C19H17FO4 280.1111; found 380.1144.

16. (a) Vu, C. S.; Guisot, N.; Guillarme, S.; Martel, A.; Dujardin, G.; Pipelier, M.;Dubreil, D.; Saluzzo, C. Eur. J. Org. Chem. 2012, 3727; (b) Wilkinson, A. L.;Hanefeld, U.; Wilkinson, B.; Leadlay, P. F.; Ataunton, J. Tetrahedron Lett. 1998,39, 9827; (c) Clissold, C.; Kelly, C. L.; Lawrie, K. W. M.; Willis, C. L. TetrahedronLett. 1997, 38, 8105.